Vascularized Bone Grafts for Tissue Engineering

用于组织工程的血管化骨移植物

基本信息

批准号：
7034319
负责人：
Edward A. Botchwey
金额：
$ 12.55万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-03-05 至 2010-12-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The candidate, Dr. Edward Botchwey, is experienced in orthopaedic biomaterials and tissue engineering. His long term career goal is to establish an independent research laboratory to pursue his interests in the development of experimental and computational methods to study the role of angiogenesis and microvascular remodeling in bone tissue engineering. His intermediate term objective is to work together with mentor Dr. Thomas Skalak, chair of biomedical engineering at the University of Virginia, to leverage the tremendous resources available at UVA to achieve this goal. This proposal outlines a career development plan to design and build new enabling technologies capable of co-cultivating osteoblastic cells and vascular endothelial cells within tissue engineered scaffolds, and varying the geometric arrangement of cells so that optimization of both bone remodeling and neo-vascularization can be explored. In vivo experimental assessment and novel computational modeling approaches will be developed to identify the geometries of combined cell distribution that are most conducive to bone healing and vascular remodeling. The specific objectives of the proposal are 1) to quantify the effects of perfusion flow velocity and internal pore network geometry on rMSC proliferation, gene expression, and mineralized deposition within 3-D microsphere based scaffolds in a customized perfusion. 2) to develop new experimental methods to co-culture rat microvascular endothelial cells (rVECs) within mineralized rMSC constructs formed in Aim1. Specifically, rVECs will be cultivated according to two predetermined geometric configurations, (a) uniformly dispersed network within the scaffolds, and (b) externally laminated layer around the scaffolds. 3) to combine experimental and computational methods to determine whether the geometric distribution of vascular endothelial cells within mineralized bone tissue engineered scaffolds developed in Aim 2 enhance microvascular network remodeling and ectopic bone formation in a customized rat window chamber model in viv.

描述（由申请人提供）：候选人 Edward Botchwey 博士在骨科生物材料和组织工程方面拥有丰富经验。他的长期职业目标是建立一个独立的研究实验室，以追求他对开发实验和计算方法的兴趣，以研究血管生成和微血管重塑在骨组织工程中的作用。他的中期目标是与导师、弗吉尼亚大学生物医学工程系主任 Thomas Skalak 博士合作，利用 UVA 的巨大资源来实现这一目标。该提案概述了一项职业发展计划，旨在设计和构建新的使能技术，能够在组织工程支架内共同培养成骨细胞和血管内皮细胞，并改变细胞的几何排列，从而优化骨重塑和新血管形成探索过。将开发体内实验评估和新颖的计算建模方法，以确定最有利于骨愈合和血管重塑的组合细胞分布的几何形状。该提案的具体目标是 1) 量化定制灌注中灌注流速和内部孔隙网络几何形状对 rMSC 增殖、基因表达和基于 3D 微球的支架内矿化沉积的影响。 2) 开发新的实验方法，在 Aim1 中形成的矿化 rMSC 构建体中共培养大鼠微血管内皮细胞 (rVEC)。具体来说，rVEC 将根据两种预定的几何构型进行培养：(a) 支架内均匀分散的网络，以及 (b) 支架周围的外部层压层。 3) 结合实验和计算方法，确定目标 2 中开发的矿化骨组织工程支架内血管内皮细胞的几何分布是否增强体内定制大鼠窗室模型中的微血管网络重塑和异位骨形成。